2021 Volume 46 Issue 1 Pages 44-55
Transforming growth factor-beta （TGF-β） is known to be an important factor for osteogenic differentiation of mesenchymal stem cells （MSCs）. We previously reported that TGF-β1 promoted the human MSC （hMSC） cell line UE7T-13 in an extracellular signal-regulated kinase （ERK）1/2-dependent manner. In addition, ascorbate, dexamethasone （Dex）, and β-glycerophosphate （β-Gp） are widely used for inducing osteogenic differentiation of osteoblast progenitor cells by activating the ERK1/2-mediated signaling pathway. Conversely, lipopolysaccharide （LPS） generally suppresses osteoblastic activity in MSCs. However, the molecular mechanisms underlying the LPSpromoted suppression of osteoblastic differentiation of hMSCs remains to be clarified. This study aimed to 1） identify key molecules that relay intracellular signals for the LPS-induced inhibition of osteogenic activity in hMSCs, and 2） investigate how TGF-β1 affects the LPS-induced inhibition of osteoblastic differentiation of hMSCs. Here, we demonstrated that LPS suppresses ascorbate-, Dex-, and β-Gp-induced osteogenic activity, but not ascorbate-, Dex-, β-Gp-, and TGF-β1-induced osteogenic activity in UE7T-13 cells. In addition, LPS suppressed ascorbate-, Dex-, and β-Gp-induced ERK activation, and partially suppressed the ascorbate-, Dex-, β-Gp-, and TGF-β1-induced ERK1/2 activation in UE7T-13 cells in a nuclear factor kappa-B （NF-κB）-dependent manner. These results suggested that TGF-β1 abrogated the LPS-induced activation of the NF- κB-mediated signaling pathway that relays the suppressive effect on the osteogenic activity of hMSCs partially by the ERK1/2-mediated signal. However, the network would be complexed, and the further research is needed to confirm this.
The present findings partially clarify the molecular mechanisms underlying the development of apical periodontitis-induced suppression of ossification around the tooth root apex, and may aid in identifying therapeutic targets for this condition.
